ワクチン接種による予防:免疫不全・低下患者
免疫機能が低下した患者におけるアジュバント組換え帯状疱疹ワクチン(RZV)の有効性、免疫原性および安全性
免疫不全・低下患者は、年齢をマッチさせた免疫健常の対照者よりも帯状疱疹のリスクが高いことが示唆されています。
下記のグラフは、文献で報告されている成人の様々な病態における帯状疱疹の発生率を要約したものです。免疫不全・低下患者は、年齢をマッチさせた免疫健常の対照者よりも帯状疱疹(HZ)のリスクが高いことが示されています。例えば、最も重度の免疫不全集団として代表される骨髄または造血幹細胞移植を受けた患者は、帯状疱疹の発症率が最も高いことが報告されています1-17。
HIV, human immunodeficiency virus.
免疫不全・低下患者集団におけるRZVの臨床試験の概要
異なる免疫不全・低下患者集団を対象とした以下の5つの臨床試験(うち4つは複数の免疫抑制剤を併用)では、RZVは強固で持続的な液性免疫反応と細胞性免疫反応を誘導しました18。
Human Immunodeficiency Virus (HIV) People living withHIV19 |
Autologous Haematopoietic Stem Cell Transplant (auHSCT) Post-autologous5 | Haematological Malignancies While on immunosuppressive chemotherapy7 |
Renal Transplants Post-renal transplant20 |
Solid Tumour Solid tumour malignancies while on immunosuppressive chemotherapy21 |
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Trial | NCT01165203* | NCT01610414† | NCT01767467 | NCT02058589 | NCT01798056 |
Phases | Phase 1/2a (N=123) |
Phase 3 (N=1846) |
Phase 3 (N=562) |
Phase 3 (N=264) |
Phase 3 (N=232) |
Trial type | Placebo-controlled, ≥18 years of age | ||||
Primary endpoints |
Reactogenicity/ Immunogenicity/ Safety |
Efficacy | Reactogenicity/ Immunogenicity/ Efficacy§ |
Immunogenicity/ Safety |
Reactogenicity/ Immunogenicity/ Safety |
Dose timeline |
Month 0, 2, 6 (3 doses) |
Month 0, 1–2 | |||
Click here for further information on NCT01165203 | Click here for further information on NCT01610414 | Click here for further information on NCT01767467 | Click here for further information on NCT02058589 | Click here for further information on NCT01798056 |
*RZV was studied in a Phase 1/2a trial in HIV patients; †a phase 1/2, randomised, observer-blind, placebo-controlled study was previously conducted to assess safety and immunogenicity of two formulations of RZV in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukaemia who had undergone autologous haematopoietic stem-cell transplant 50 to 70 days earlier; §efficacy was evaluated in a post hoc analysis.7
References: 5. Bastidas A, et al. JAMA. 2019;322(2):123–133; 7. Dagnew AF, et al. Lancet Infect Dis. 2019;19(9):988–1000; 19. Berkowitz EM, et al. J Infect Dis. 2015;211(8):1279–1287; 20. Vink P, et al. Clin Infect Dis. 2020;70(2):181–190; 21. Vink P, et al. Cancer. 2019;125(8):1301–1312.
auHSCT, autologous haematopoietic stem cell transplant; HIV, human immunodeficiency virus; RZV, recombinant zoster vaccine.
結論
様々な免疫不全・低下患者を含む5つの無作為化プラセボ対照試験において、RZVは強固で持続的な体液性および細胞性免疫応答を誘導しました。
HZに対する防御のメカニズムである細胞性免疫反応は、基礎疾患がある状態においても、少なくとも1年間は、50歳以上の正常な免疫機能を有する成人で観察されたレベルと同程度に維持されました。さらに、年齢(18-49歳または50歳以上)は、auHSCT、血液悪性腫瘍、腎移植、固形腫瘍の患者における細胞性免疫反応の大きさに影響を与えませんでした。
auHSCT患者では68.2%、血液悪性腫瘍患者ではPost-hoc Analysisにおいて87.2%の有効性が示されました。固形がん患者や腎移植患者に対する有効性データはありませんが、細胞性免疫反応はauHSCT患者や血液悪性腫瘍患者における試験結果と同等であり、同様の臨床的ベネフィットが示されました5,7,18-21。
Abbreviations
AE, adverse event; ART, anti-retroviral therapy; ATP, according to protocol; BCL, B-cell lymphoma; CLL, chronic lymphocytic leukaemia; CMI, cell-mediated immunity; gE, glycoprotein E; GI, gastrointestinal; GMC, geometric mean concentration; HIV, human immunodeficiency virus; IQR, interquartile range; LL, lower limit; Mo, month; mTVC, modified total vaccinated cohort; pIMD, potential immune-mediated disease; PHN, post-herpetic neuralgia; Pre, pre-vaccination; Q, quartile; RZV, recombinant zoster vaccine; SAE, serious adverse event; TVC, total vaccinated cohort; UL, upper limit; VE, vaccine efficacy; VRR, vaccine response rate; YOA, years of age
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NX-JP-SGX-WCNT-230008 | October 2023